Title : A unique C-terminal
domain allows retention of
matrix metalloproteinase-27 in the endoplasmic reticulum
Abstract :
- Matrix metalloproteinase-27 ( MMP-27 ) is poorly characterized
- Sequence comparison suggests that a C-terminal extension (CTE) includes a potential transmembrane domain as in some membrane-type (MT)-MMPs
- Having noticed that MMP-27 was barely secreted, we investigated its subcellular localization and addressed CTE contribution for MMP-27 retention
- Intracellular MMP-27 was sensitive to endoglycosidase H. Subcellular fractionation and confocal microscopy evidenced retention of endogenous MMP-27 or recombinant rMMP-27 in the endoplasmic reticulum (ER) with locked exit across the intermediate compartment (ERGIC)
- Conversely, truncated rMMP-27 without CTE accessed downstream secretory compartments (ERGIC and Golgi) and was constitutively secreted
- CTE addition to rMMP-10 (a secreted MMP) caused ER retention and blocked secretion
- Addition of a PKA target sequence to the cytosolic C-terminus of transmembrane MT1-MMP / MMP-14 led to effective phosphorylation upon forskolin stimulation, but not for MMP-27 , excluding transmembrane anchorage
- Moreover, MMP-27 was protected from digestion by proteinase K. Finally, MT1-MMP / MMP-14 but neither endogenous nor recombinant MMP-27 partitioned in the detergent phase after Triton X-114 extraction, indicating that MMP-27 is not an integral membrane protein
- In conclusion, MMP-27 is efficiently retained within the ER due to its unique CTE, which does not lead to stable membrane insertion
- This could represent a novel ER retention system
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
- 2. membrane-type (MT)-MMPs, domain
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):